Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity - PubMed (original) (raw)
Review
. 2004 Mar;111(3):347-66.
doi: 10.1007/s00702-003-0058-y. Epub 2003 Dec 12.
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- PMID: 14991459
- DOI: 10.1007/s00702-003-0058-y
Review
Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity
M Weinstock et al. J Neural Transm (Vienna). 2004 Mar.
Abstract
Three models are described in rats which attempt to mimic morphological and behavioural pathology of Alzheimer's dementia; intracerebroventricular injection of streptozotocin (STZ), permanent bilateral carotid artery occlusion (2VO) and brain mitochondrial cytochrome oxidase inhibition by sodium azide. Learning and memory are impaired within 4 weeks in all models. This probably involves a reduction in cortical and/or hippocampal cholinergic neurotransmission. STZ causes microglial activation and specific damage to myelinated tracts in the fornix through generation of oxidative stress, thereby disrupting connections between the septum and hippocampus. 2VO results in damage to myelin and CA1 cells in hippocampus and in abnormal processing of APP to beta-amyloid. It is not known if microglial activation and neuronal damage occur after sodium azide administration. Memory and learning can be improved in the STZ and 2VO models by estradiol, melatonin and cholinesterase inhibitors. Antioxidants and neuroprotective agents may also decrease memory deficits by preventing inflammation and neurodegeneration.
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